tbuckley/cabot-search huggingface dataset:
Abstract 12514: Direct Oral Anticoagulants versus Warfarin for Preventing Thromboembolic Events in Valvular Heart Diseases Associated Atrial Fibrillation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Amira Mohamed Taha, Ahmed Mohamed, Yasmeen Abdelglel Mohamed, Esraa Hamouda, Fatmaelzahraa yasser ali, Mohamed Hamouda Elkasaby, Youssef Soliman, Yusra Nasir, Vikash Jaiswal, Amr Elrosasy
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) and valvular heart disease (VHD) are common comorbidities, increasing the risk of thromboembolic events. While warfarin has been the standard for preventing stroke in AF patients, direct oral anticoagulants (DOACs) have emerged as an effective substitute. However, their safety and efficacy in VHD patients have yet to be established. Objective: To compare the effectiveness and safety of different DOAC agents versus warfarin in patients with AF and VHD in a network meta-analysis (NMA). Methods: We conducted an online search of databases for eligible studies from inception to April 2023. For dichotomous variables, we calculated the effect size using the risk ratio (RR) and its confidence interval (CI). We conducted frequentist and pairwise meta-analyses using the random-effects model in R-studio software. Results: Seven randomized controlled trials with 17533 patients were included in the review. Analysis of 6 studies showed that dabigatran 150 mg (RR 0.59, 95% CI [0.36, 0.98]) was associated with a lower risk of stroke compared to warfarin. Edoxaban 30 mg was associated with a significantly lower risk of major bleeding (RR 0.43, 95 CI [0.23, 0.81]). Compared to warfarin, dabigatran 110 mg (RR 0.29, 95% CI [0.13, 0.68]), edoxaban 30 mg (RR 0.30, 95% CI [0.11, 0.80]), dabigatran 150 mg (RR 0.36, 95% CI [0.17, 0.77]), edoxaban 60 mg (RR 0.37, 95% CI [0.15, 0.93]), and apixaban (RR 0.40, 95% CI [0.27, 0.61]), were associated with a significantly lower risk of intracranial hemorrhage (ICH). All DOACs did not show any difference in terms of all-cause or cardiovascular mortality, except for rivaroxaban Conclusion: In patients with AF and VHD, Edoxaban 30 mg is the safest DOAC agent associated with a reduced risk of major bleeding, ICH, and GI trouble. Dabigatran 150 mg is associated with a reduced risk of stroke and ICH but with a higher risk of GI trouble. However, Rivaroxaban is associated with an increased risk of systemic embolism.
Abstract 16926: Associations of Preeclampsia and Preterm Delivery With Lifetime Posttraumatic Stress
Authors: Jennifer J Stuart, Janet W Rich-Edwards, Karestan C Koenen, Kathryn M Rexrode
Journal: Circulation (2023)

Introduction: Adverse pregnancy outcomes (APOs) are female-specific CVD risk factors while posttraumatic stress disorder (PTSD) is a female-predominant CVD risk factor. Preeclampsia and preterm delivery are acute APOs with negative maternal and fetal consequences that, for some, results in trauma. Hypothesis: We hypothesized that individuals with a history of preeclampsia or preterm delivery would be more likely to screen positive for lifetime PTSD. Methods: Parous Nurses’ Health Study II participants who responded to a 2008 questionnaire ascertaining trauma (Brief Trauma Questionnaire, with targeted query of 16 event types) and PTSD (Short Screening Scale for DSM-IV PTSD) comprised the analytic sample (n=40,256). Trauma and PTSD were categorized using four categories: no trauma, trauma with no PTSD symptoms, 1-3 symptoms, or ≥4 symptoms (probable PTSD). Ordered logistic regression, using a cumulative logit link and multinomial distribution, estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for age at enrollment, race/ethnicity, and parental education. Results: Seven percent of participants had a history of preeclampsia (n=3,012) while 13.5% (n=5,418) ever delivered preterm. Twenty-one percent of participants screened positive for PTSD (n=8,336), endorsing ≥4 symptoms from their worst trauma. Among participants with PTSD, 66% of those with preterm preeclampsia in their first pregnancy endorsed having a traumatic pregnancy complication or labor/birth, compared to 23% among those who delivered normotensive first pregnancies at term. Odds of PTSD were higher with history of ever preeclampsia (OR=1.36, CI: 1.27-1.45) or preterm delivery (OR=1.41, CI: 1.34-1.48), compared to only normotensive pregnancies and term deliveries, respectively. Further adjustment for physical or sexual abuse in childhood/adolescence did not change conclusions but did attenuate the odds ratio for preeclampsia (OR=1.26, CI: 1.18-1.35). Conclusions: History of preeclampsia or preterm delivery identifies a population at higher risk for lifetime posttraumatic stress. Further studies are needed to disentangle temporality and examine to what extent subsequent mental health conditions may mediate the relationship between APOs and CVD.
Abstract 16901: A Computational Framework to Estimate the Consequences of Cardiac RNA Editing Events at Single-Cell Resolution
Authors: Prashant Srivastava, Mohamed Hassani, Jiahui Ji, Yingshu Guan, Prakash Punjabi, Costanza Emanueli
Journal: Circulation (2023)

Introduction: RNA is a highly dynamic molecule subject to various epigenetic modifications. One such process is RNA editing, a tightly regulated mechanism that introduces alterations to RNA nucleotides without affecting the DNA template. RNA editing serves as a mechanism for expanding and diversifying the functional repertoire of proteins. In the context of the heart, the RNA editors assume crucial roles in preserving cardiac function. Despite the importance of RNA editing, there are no framework to evaluate consequence of synonymous RNA editing events. Synonymous RNA editing events can affect mRNA stability, translation efficiency, protein folding, and even protein-protein interactions. These subtle changes in the coding region can influence gene expression, protein synthesis, and ultimately, cellular function. Research question: What are the functional consequences of RNA editing events in different types of cardiac cells? Methods: To estimate the RNA structural metrics, we employed the Vienna RNA package software. This comprehensive package provides a range of metrics for quantifying RNA secondary structures. Results: We have developed a framework to profile RNA editing and analyse synonymous events using new and existing single-cell datasets. Our framework enables users to explore the distribution of RNA editing events across different cell types and states, as well as analyse the functional consequences of these events. Here, to demonstrate its efficacy, we have applied our framework on healthy hearts. We identified highly edited cell types such as cardiomyocytes, fibroblasts, endothelial cells, macrophages, and pericytes, with over 1,000 edited sites. Interestingly, more than 50% of these edited sites enhanced secondary RNA structures, while 25% of the events destabilized the secondary structure. Conclusions: We have developed a comprehensive framework to estimate consequence of RNA editing events at single-cell resolution. Our results demonstrate the power of our framework in elucidating the impact of RNA editing on cellular processes. Synonymous RNA editing expands our understanding of the complexity of genetic regulation and its implications for cellular processes and disease.
Abstract 13812: Daily Marijuana Use is Associated With Incident Heart Failure: “All of Us” Research Program
Authors: Yakubu Bene-Alhasan, Albert D Osei, Anita Tammara, Omar Almaadawy, Matthew Dwumah-Agyen, Samuel Mensah, Bethel Woldu
Journal: Circulation (2023)

Background: With the increasing state-level legalization of marijuana across the United States, its use has increased exponentially, especially among the youth. However, a lot remains unknown concerning its cardiovascular health implications. We sought to assess the association between the frequency of marijuana use and new-onset heart failure (HF). Methods: Using the NIH-sponsored “All of Us” Research Program, we performed a prospective analysis of participants’ survey data and Electronic Health records (EHR). We excluded patients with a baseline EHR diagnosis of HF. Marijuana use was defined as any unprescribed use or if prescribed, use beyond prescribed doses, and was collected using the NM ASSIST instrument. We determined the association between the frequency of marijuana use and incident HF using Cox proportional hazards models adjusted for demographic and socioeconomic factors, diabetes mellitus, hypertension, hyperlipidemia, BMI, alcohol use and smoking status. Results: From a final population of 156,999, there were 2958 events within a median follow-up time of 45 months. Compared to never users, daily marijuana users had an increased risk of incident HF (aHR - 1.34, 95% CI 1.04-1.72). In subgroup analyses, frequency of marijuana use was not associated with incident HFrEF nor HFpEF. There was no evidence of effect modification by age, sex at birth nor smoking status. The relationship was attenuated after addition of coronary artery disease diagnosis as a time varying covariate in our main model (aHR - 1.27, 95% CI 0.99-1.62). Implication: Data on the cardiovascular effects of marijuana use is limited. To our knowledge this is the first prospective analysis on the association of marijuana use and HF. Our study suggests daily marijuana use is associated with HF. More research into the cardiovascular effects of marijuana is needed to enable clinicians provide the public with high quality information on the health implications of marijuana and to guide policies.
Abstract 12587: Cardiac Tamponade and Pericardial Effusion in a Patient With Stage 3 Malignant Melanoma Treated With Pembrolizumab
Authors: Daniel A Ubokudom, Ovie Okorare, Unwam Jumbo
Journal: Circulation (2023)

Introduction: The introduction of immunotherapy has revolutionized the treatment of cancer, with improved clinical outcomes. One of such agents include Pembrolizumab a humanized antibody which acts as an immune check point inhibitor by binding to Programmed cell death Protein 1 receptors. One principal setback is its autoimmune-dysfunctional side effect. Case Presentation: A 74-year-old male with BRAF-negative malignant melanoma status post resection, with recurrent neoplasm involving lymph nodes of the base of the left neck presented to the emergency department with palpitations, diarrhea and difficulty in breathing. Symptoms began three weeks after his fourth course of adjuvant therapy. On presentation he was hemodynamically unstable with positive Kussmaul sign on examination. His heart sounds were muffled, with clear lung bases bilaterally. Results of EKG and echo are has shown below. Decision-Making: Patient was commenced on Intravenous fluid normal saline, oxygen therapy, was evaluated by cardiology and had emergency pericardiocentesis with about 250mls of fluid drained from the pericardial cavity and improvement of symptoms. Pericardial fluid analysis showed acute inflammation without malignant cells. Patient was placed on steroids and a consensus was reached to discontinue Pembrolizumab and pursue other lines of treatment as determined by the hospital tumor board. Discussion: The exact incidence of pericardial disease in cancer patients treated with Immune check inhibitors including Pembrolizumab is unknown. When effusion occurs, urgent intervention should be performed to prevent life threatening cardiac events. Treatment with steroids has shown improved outcomes and should be encouraged. Conclusion: Pericardial effusion is a fatal complication of Pembrolizumab. Though incidence remains rare, a high index of suspicion should be maintained in Patients receiving this immune check point inhibitor. The Decision to continue therapy after a cardiovascular event such as Pericardial Effusion should be individualized.
Abstract 13851: CAR-T Cells: A Potential Novel Strategy for Mitigating Fibrosis in Duchenne Muscular Dystrophy
Authors: Celine Marigny, Gaelle Revet, Anne Berger, Morgane Boulch, Nathalie Mougenot, Axelle Bois, Victor Collombat, Sabrina Bousta, Mégane Lemaitre, Adrian Bot, Peggy Lafuste, Albert Hagege, Haig Aghajanian, Philippe Bousso BOUSSO, Onnik Agbulut, Philippe Menasche
Journal: Circulation (2023)

Introduction: Chimeric Antigen T (CAR)-T cells have proven effective preclinically for mitigating cardiac fibrosis in hypertensive cardiomyopathy. Hypothesis: We assessed whether this approach could be applied to Duchenne Muscular Dystrophy (DMD) by targeting Fibroblast Activating Protein (FAP)-expressing activated fibroblasts in cardiac and skeletal muscle fibrosis. Methods: A protocol for the lymphodepletion conditioning of mice was developed to optimize the dosing of cyclophosphamide. Next, immune-magnetically selected T cells were retrovirally transduced to target FAP (FAP-CAR) and quality-controlled by co-culture killing assays using FAP-expressing HEK target cells. Finally, lymphodepleted D2. mdx mice were intravenously injected with 10 7 FAP-CAR T cells (n=9) or 10 7 GFP-T cells (n=9) or Bovine Serum Albumin (BSA, n=8). Cardiac and skeletal muscle end points were assessed 2 and 5 weeks after treatment. Results: In vitro , the engineered CAR-T cells expressed activation markers (CD69, PD-1) and released large amounts of granzyme, perforin and interferon γ upon exposure to FAP-expressing target cells. One IP injection of cyclophosphamide (3mg) 4 days before treatment was safe and induced a lymphodepletion which enabled robust in vivo expansion of FAP-CAR T cell assessed by flow cytometry in lymphoid organs and blood: 10 5 , 2.10 6 and 10 7 detected CAR-T cells at day 3, 5 and 7 post-injections, respectively. This was paralleled by a more than a 2-fold decrease in endogenous FAP expression in skeletal muscles, as assessed by PCR at day 5 post-injections, and measurable FAP-CAR levels in the spleen compared with GFP-T cell controls. In vivo , FAP-CAR T cells significantly improved LV function with an EF change from baseline (Mean±SEM) of 33.1% ± 6.7% in FAP-CAR vs. 3.7% ± 6.4% and -9.6% ± 7.9% in GFP-T and BSA ( p &lt;0.037 and p &lt;0.005, respectively) at 2 weeks. The benefit was maintained at 5 weeks post-treatment. Several markers of fibrosis, particularly collagens 1 and 3, were also down-regulated in heart and muscles. Conclusions: FAP-CAR-T cells might represent a new therapeutic option for mitigating fibrosis in DMD, likely in conjunction with approaches aimed at addressing the root cause of the disease through a re-expression of a functional dystrophin.
Abstract 13850: Cost-Effectiveness Analysis of Universal Screening for Atrial Fibrillation Using Electrocardiographic Artificial Intelligence in a Rural Community in Taiwan
Authors: Wei-Ting Liu, Chin-Sheng Lin, CHIN LIN, Ping-Hsuan Hsieh
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) substantially contributes to strokes, and screening for AF is generally recommended. However, implementing universal screening for AF is challenging in rural areas with limited medical resources. This study assessed the cost-effectiveness of using artificial intelligence-enabled 12-lead electrocardiography (AI-ECG) for AF screening in a rural community. Methods: The cost-effectiveness analysis focused on screening individuals aged 65 or older and utilized a lifelong decision analytic Markov model. The AI-ECG for AF was trained at a medical center in Taiwan, achieving a sensitivity of 0.944 (standard error [SE]: 0.015) and specificity of 0.941 (SE: 0.008). Costs and efficacy of anticoagulant treatments, utility of health status, and clinical variables such as stroke and major bleeding risks were estimated based on literature and epidemiological data from Taiwan. Results were presented as US dollars per quality-adjusted life year (QALY). The base-case analysis compared technicians using AI-ECG for AF detection and referral, and physicians' evaluation with standard 12-lead ECGs to no screening. Uncertainty in the model was addressed through probabilistic sensitivity analysis. Results: Both AI-ECG screening and screening by a physician were found to be more costly yet more effective when compared to no screening. While both strategies exhibited similar effectiveness, the cost was lower with AI-ECG than by a physician ($453 versus $490). Based on 10,000 Monte Carlo simulations, if the willingness to pay (WTP) for a QALY exceeds $9,514, screening by a physician is a cost-effective strategy. However, if the WTP per QALY falls between $2,289 and $9,514, AI-ECG screening is more cost-effective than physician-based screening. Conclusion: This economic evaluation demonstrates the cost-effectiveness of AI-ECG screening for AF, making it a practical alternative for AF screening in areas with limited medical resources.
Abstract 13874: N Terminal Pro-Brain Natriuretic Peptide Levels and Benefits of Chronic Total Occlusion Revascularization
Authors: Daniel A Gold, Pratik B Sandesara, Vardhmaan Jain, Matthew E Gold, Nishant Vatsa, Shivang Desai, Malika Elhage Hassan, Chenyang Yuan, Yi-An Ko, Chang Liu, Kiran Ejaz, Zain N Alvi, Ayman Alkhoder, Alireza Rahbar, Gillian Murtagh, Christos Varounis, Wissam Jaber, William Nicholson, Arshed A Quyyumi
Journal: Circulation (2023)

Background: The management of chronic total occlusion (CTO) remains a subject of debate, as the mortality benefit from revascularization remains controversial. Whether specific populations gain a survival benefit from CTO revascularization remains unknown. Purpose: In this prospective study of patients with stable coronary artery disease (CAD), we investigated whether patients with CTO have higher adverse event rates and higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO. We also investigated whether a higher NT pro-BNP level predicts adverse events in patients with CTO and whether those with elevated NT pro-BNP levels have a survival benefit from revascularization. Methods: In 2,253 patients with significant CAD ( &gt; 50% coronary luminal stenosis) undergoing cardiac catheterization, all-cause mortality, cardiovascular mortality and the composite of cardiovascular death, myocardial infarction and heart failure hospitalization rates were evaluated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP level and event rates. Results: Patients with CTO had higher incident event rates by &gt; 20% and had higher NT pro-BNP levels than those without CTO (median 230.0 vs. 177.7 pg/mL, p=&lt;0.001). In patients with CTO, every doubling of NT pro-BNP level was associated with &gt; 25% greater risk of adverse events. In patients with elevated NT pro-BNP level (&gt; 125 pg/mL), CTO revascularization was associated with &gt;50% lower adverse event rates than those without CTO revascularization (adjusted cardiovascular death hazard ratio 0.24, 95% confidence interval 0.07 - 0.81). Among patients with low NT pro-BNP level (&lt; 125 pg/mL), event rates were similar in those with and without CTO revascularization. Conclusion: Patients with CTO have higher adverse event rates than those with significant CAD without CTO. NT pro-BNP levels are higher in patients with CTO and higher levels portend a worse prognosis. Moreover, NT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.
Abstract 13821: Induction of Immune Tolerance to Intramyocardial Transplantation of Cardiac Progenitor Cells by Regulatory T Lymphocytes
Authors: Aline Derisio de Lima, Hernán G Garibotti, Myriam Assal, Aness Haddouche, VALERIE BELLAMY, Qing Dong Wang, Cecilia Graneli, Makoto Miyara, Jean-Sebastien Silvestre, Karin Jennbacken, Philippe Menasche
Journal: Circulation (2023)

Introduction: The clinical use of human embryonic stem cell (hESCs)-derived cardiac cells is still hampered by rejection which is managed by immunosuppressive drugs and exposes to their side-effects. Hypothesis: We evaluated an alternate strategy based on the induction of immune tolerance by adoptive regulatory T lymphocytes (Treg) transfer. Methods: Human hTreg were isolated from peripheral blood mononuclear cells, expanded for 9 days and phenotyped. Immune-competent mice were then subjected to a myocardial infarction. Three weeks later (baseline), mice with an echocardiographically-measured ejection fraction (EF) ≤50% underwent trans-cutaneous echo-guided peri-infarct injections of 1.4x10 6 hESC-cardiovascular progenitor cells (CPC; n=11) or an equivalent volume of PBS (controls, n=4). Among the CPC-transplanted mice, 6 were intravenously injected with 2x10 6 hTreg at the time of transplantation and 3 days later and 5 only received the vehicle (PBS). Functional and histological end points were assessed 3 weeks after treatments (final) and spleen tissue was processed by flow cytometry for the evaluation of immune cell populations. Results: Three weeks after treatments, all CPC-transplanted hearts had a significantly better preservation of EF [m±SEM], compared with their respective baseline values, than PBS-injected hearts (35.4% ± 5.4% in CPC and 37.5% ± 6.8% in CPC+hTreg vs. -1.3 ± 7.3% in PBS, p=0.004) which was mainly driven by a reduction in LV end-systolic volumes (p=0.004) but only in the hTreg group global longitudinal strain improved by 15.7% ± 13.3% from baseline while it worsened by 36.5% ± 18.8% in their non-hTreg counterparts (p=0.037). Infarct size did not differ among the 3 groups but Treg reduced interstitial fibrosis in remote non infarcted myocardium (0.6% ± 0.1%, p=0.007 vs. CPC-non hTreg and PBS, respectively) and, in spleen tissue, induced significant decreases in CD80+ M1 macrophages (p=0.010) and NKG2D+ NK cells (p=0.013) and an increase in CD206+ M2 macrophages (p=0.004) compared with the other 2 groups. Conclusions: Systemic hTreg administration mitigates adverse heart remodeling by modulating the immune response, potentially facilitating transplantation of hESC-CPC with reduced immunosuppression requirements.
Abstract 12594: Comparison of Effects of Face-to-Face and Online Community-Based Healthy Lifestyle Behavior Change Programs on Life Simple 7 Score in the Elderly
Authors: Tsueyyuan Huang, Ming-Fen Tsai, Debra K Moser
Journal: Circulation (2023)

Introduction: The Life Simple 7 (LS7) score, developed by the American Heart Association, is a powerful predictor of an individual's cardiovascular health. It consists of seven key cardiovascular health metrics, including cholesterol levels, blood pressure, blood sugar, body mass index, diet, smoking status, and physical activity levels. In-person behavior change programs that target LS7 may not be accessible to older people. Aims: Our aim was to compare the impact of face-to-face and online community-based programs on the LS7 score among elderly individuals. Methods: Elderly participants were recruited from local community centers and randomly assigned to either a face-to-face or online program group. The face-to-face group attended weekly sessions at the community center, while the online group received program content through a web-based platform. Changes in the LS7 score were measured at baseline and six weeks after the intervention. An analysis of covariance (ANCOVA) was used to compare outcomes. Results: A total of 114 elderly individuals, with an average age of 71.75 ± 10.39 and 70.8% males, participated in the study (face-to-face group, n=48; online group, N=66. The findings indicate significant improvements in blood pressure (p=0.048), cholesterol (p=0.021), exercise (p=0.000), and diet scores (p=0.001). However, no significant differences were observed between the two groups (F=0.16, p&gt;.05). Conclusion: The findings suggest that both modes of intervention are effective in improving cardiovascular health, highlighting the potential of online programs during times such as the COVID-19 pandemic or in rural areas.